The molecular bases of three classes of inherited corneal disease are to be examined by locating and isolating the disease-causing genes. This application builds upon strong preliminary data including the genetic linkage of three clinically distinct autosomal dominant corneal dystrophies to the long arm of chromosome 5 and the linkage of posterior polymorphous corneal dystrophy to the long arm of chromosome 20. The specific aims are to (1) use position candidate and positional cloning strategies to identify the gene involved in Avelino, granular and lattice corneal dystrophies; (2) perform a genome-wide search for linkage in families affected with Fuch's corneal dystrophy; and (3) refine the genetic interval on chromosome 20q that contains the posterior polymorphous dystrophy locus and use the positional candidate strategy to search for the disease-causing gene.